H-Arg-Pro-Tyr-Gly(tBu)-Leu-OH | 1142814-19-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: H-Arg-Pro-Tyr-Gly(tBu)-Leu-OH
• 英文别名: (2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3,3-dimethylbutanoyl]amino]-4-methylpentanoic acid
• CAS: 1142814-19-4
• 化学式: C₃₂H₅₂N₈O₇
• 分子量: 660.814
• InChiKey: HYZRLEYRWNUYNM-KFEALIJWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.4
• 重原子数：
  47
• 可旋转键数：
  17
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  256
• 氢给体数：
  8
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  ABS-212 在 水 作用下， 生成 H-Arg-Pro-Tyr-Gly(tBu)-Leu-OH 、 H-Pro-Tyr-Gly(tBu)-Leu-OH 、 H-Arg-Pro-Tyr-Gly(tBu)-OH 、 [(4S)-5-[[(2S)-1-[(2S)-2-[[(1S)-1-carboxy-2-(4-hydroxyphenyl)ethyl]carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-5-oxopentyl]-trimethylazanium;2,2,2-trifluoroacetate 、 [(4S)-5-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(1S)-1-carboxy-2,2-dimethylpropyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-5-oxopentyl]-trimethylazanium;2,2,2-trifluoroacetate
  参考文献：
  名称：

  Identification and Functional Characterization of a Stable, Centrally Active Derivative of the Neurotensin (8−13) Fragment as a Potential First-in-Class Analgesic

  摘要：

  The neurotensin hexapapetide fragment NT(8-13) is a potent analgesic when administered directly to the central nervous system but does not cross the blood brain barrier. A total of 43 novel derivatives of NT(8-13) were evaluated, with one, ABS212 (1), being most active in four rat models of pain when administered peripherally. Compound 1 binds to human neurotensin receptors 1 and 2 with IC50 of 10.6 and 54.2 nM, respectively, and tolerance to the compound in a rat pain model did not develop after 12 days of daily administration. When it was administered peripherally, serum levels and neurotensin receptor binding potency of 1 peaked within 5 min and returned to baseline within 90-120 min; however, analgesic activity remained near maximum for > 240 min. This could be due to its metabolism into an active fragment; however, all 4- and 5-mer hydrolysis products were inactive. This pharmacokinctic/pharmacodynamic dichotomy is discussed. Compound 1 is a candidate for development as a first-in-class analgesic.

  DOI：

  10.1021/jm100092s